Oncodevelopmental regulation of the alternative splicing of fibronectin pre-messenger RNA in human lung tissues.
Alternative splicing of fibronectin pre-mRNA at the ED-A region has been shown to be deregulated in malignant human liver tumors (F. Oyama et al., J. Biol. Chem., 264: 10331-10334, 1989). In order to extend this observation to other human cancers, we investigated the splicing patterns of fibronectin pre-mRNA at both ED-A and ED-B regions in normal, fetal, and cancerous lung tissues. Unlike in the liver, the ED-A+ mRNA was constitutively expressed in the lung irrespective of ontogenic or oncogenic stages. Although fetal tissues expressed the ED-A+ mRNA slightly more than did adult tissues, there was virtually no significant difference between malignant and nonmalignant tissues in the level of the ED-A+ mRNA. In contrast, significant expression of the ED-B+ mRNA was observed with fetal and cancerous tissues but not with normal adult tissues. Increased expression of the ED-B+ mRNA was associated with all types of lung cancer including adenocarcinoma, squamous cell carcinoma, small cell carcinoma, and large cell carcinoma. These results indicate that it is the ED-B, but not the ED-A, region where the alternative splicing of fibronectin pre-mRNA is oncodevelopmentally regulated in the lung. Our results also suggest that deregulation of the tissue-specific alternative splicing of fibronectin pre-mRNA is not a unique phenotype of liver cancer but rather a general feature of naturally occurring human cancer.
Oyama
F
F
Institute for Comprehensive Medical Science, Fujita Health University School of Medicine, Aichi, Japan.
Hirohashi
S
S
Shimosato
Y
Y
Titani
K
K
Sekiguchi
K
K
D000818:Animals; D015342:DNA Probes; D005333:Fetus; D005353:Fibronectins / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D012326:RNA Splicing; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics
D015342:DNA Probes; D005353:Fibronectins; D012333:RNA, Messenger